Abstract

Natural killer (NK) cells are critical to both innate and adaptive immunity. However, the development and heterogeneity of human NK cells are yet to be fully defined. Using single-cell RNA-sequencing technology, here we identify distinct NK populations in human bone marrow and blood, including one population expressing higher levels of immediate early genes indicative of a homeostatic activation. Functionally matured NK cells with high expression of CX3CR1, HAVCR2 (TIM-3), and ZEB2 represents terminally differentiated status with the unique transcriptional profile. Transcriptomic and pseudotime analyses identify a transitional population between CD56bright and CD56dim NK cells. Finally, a donor with GATA2T354M mutation exhibits reduced percentage of CD56bright NK cells with altered transcriptome and elevated cell death. These data expand our understanding of the heterogeneity and development of human NK cells.

Details

Title
Heterogeneity of human bone marrow and blood natural killer cells defined by single-cell transcriptome
Author
Yang, Chao 1 ; Siebert, Jason R 1 ; Burns, Robert 2 ; Gerbec, Zachary J 1 ; Bonacci, Benedetta 3 ; Rymaszewski, Amy 4   VIAFID ORCID Logo  ; Rau, Mary 5 ; Riese, Matthew J 6 ; Rao, Sridhar 7   VIAFID ORCID Logo  ; Carlson, Karen-Sue 8 ; Routes, John M 4 ; Verbsky, James W 4 ; Thakar, Monica S 9 ; Subramaniam Malarkannan 10   VIAFID ORCID Logo 

1  Laboratory of Molecular Immunology and Immunotherapy, Blood Research Institute, Versiti, Milwaukee, WI, USA; Departments of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, WI, USA 
2  Bioinfomatics Core, Blood Research Institute, Versiti, Milwaukee, WI, USA 
3  Flow Cytometry Core, Blood Research Institute, Versiti, Milwaukee, WI, USA 
4  Departments of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA 
5  Departments of Surgery, Medical College of Wisconsin, Milwaukee, WI, USA 
6  Departments of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, WI, USA; Laboratory of Lymphocyte Biology, Blood Research Institute, Versiti, Milwaukee, WI, USA; Departments of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA 
7  Departments of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA; Laboratory of Stem Cell Transcriptional Regulation, Blood Research Institute, Versiti, Milwaukee, WI, USA; Departments of Cell Biology, Neurobiology, and Anatomy, Medical College of Wisconsin, Milwaukee, WI, USA 
8  Departments of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA; Laboratory of Coagulation Biology, Blood Research Institute, Versiti, Milwaukee, WI, USA 
9  Laboratory of Molecular Immunology and Immunotherapy, Blood Research Institute, Versiti, Milwaukee, WI, USA; Departments of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA 
10  Laboratory of Molecular Immunology and Immunotherapy, Blood Research Institute, Versiti, Milwaukee, WI, USA; Departments of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, WI, USA; Departments of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA; Departments of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA 
Pages
1-16
Publication year
2019
Publication date
Sep 2019
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-019-11947-7
ProQuest document ID
2283277683
Copyright
© 2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.